Shiga Toxin (Stx)-Binding Glycosphingolipids of Primary Human Renal Cortical Epithelial Cells (pHRCEpiCs) and Stx-Mediated Cytotoxicity

Detzner J, Krojnewski E, Pohlentz G, Steil D, Humpf HU, Mellmann A, Karch H, Müthing J

Forschungsartikel (Zeitschrift) | Peer reviewed

Zusammenfassung

Human kidney epithelial cells are supposed to be directly involved in the pathogenesis of the hemolytic-uremic syndrome (HUS) caused by Shiga toxin (Stx)-producing enterohemorrhagicEscherichia coli(EHEC). The characterization of the major and minor Stx-binding glycosphingolipids (GSLs) globotriaosylceramide (Gb3Cer) and globotetraosylceramide (Gb4Cer), respectively, of primary human renal cortical epithelial cells (pHRCEpiCs) revealed GSLs with Cer (d18:1, C16:0), Cer (d18:1, C22:0), and Cer (d18:1, C24:1/C24:0) as the dominant lipoforms. Using detergent-resistant membranes (DRMs) and non-DRMs, Gb3Cer and Gb4Cer prevailed in the DRM fractions, suggesting their association with microdomains in the liquid-ordered membrane phase. A preference of Gb3Cer and Gb4Cer endowed with C24:0 fatty acid accompanied by minor monounsaturated C24:1-harboring counterparts was observed in DRMs, whereas the C24:1 fatty acid increased in relation to the saturated equivalents in non-DRMs. A shift of the dominant phospholipid phosphatidylcholine with saturated fatty acids in the DRM to unsaturated species in the non-DRM fractions correlated with the GSL distribution. Cytotoxicity assays gave a moderate susceptibility of pHRCEpiCs to the Stx1a and Stx2a subtypes when compared to highly sensitive Vero-B4 cells. The results indicate that presence of Stx-binding GSLs per se and preferred occurrence in microdomains do not necessarily lead to a high cellular susceptibility towards Stx.

Details zur Publikation

FachzeitschriftToxins
Jahrgang / Bandnr. / Volume13
Ausgabe / Heftnr. / Issue2
StatusVeröffentlicht
Veröffentlichungsjahr2021 (12.02.2021)
Sprache, in der die Publikation verfasst istEnglisch
DOI10.3390/toxins13020139
StichwörterEHEC; STEC; Shiga toxin; Stx1a; Stx2a; glycolipids; kidney cortical epithelial cells; pHRCEpiCs; receptor

Autor*innen der Universität Münster

Detzner, Johanna
Institut für Hygiene
Humpf, Hans-Ulrich
Professur für Lebensmittelchemie (Prof. Humpf)
Karch, Helge
Institut für Hygiene
Mellmann, Alexander
Institut für Hygiene
Müthing, Johannes
Institut für Hygiene